Effect of conjugated linoleic acid on body composition

A large part of the studies so far developed has been carried out using animal models and only a few intervention studies on humans have been reported. Earlier studies on animals and on humans were done using a

Table 12.4 Content of CLA (% of total fatty acids) and 10t,12c-18:2 isomer (% of CLA) in supplements sampled in 2002 (adapted from Saebo, 2003)

Product

Country

CLA (%)

10t,12c (%)

1

Norway

80.1

47.8

2

Norway

78.6

47.1

3

Norway

69.1

46.7

4

Norway

78.3

48.7

5

Norway

76.4

46.6

6

USA

71.4

46.3

7

USA

74.8

43.1

8

USA

77.9

48.5

9

USA

70.8

44.4

10

USA

79.6

45.3

11

USA

72.0

44.4

12

USA

74.3

43.6

13

USA

61.5

28.5

14

USA

76.3

48.4

15

USA

1.2

47.8

16

South Africa

51.7

16.5*

17

Norway

57.7

29.9*

* Contains 16.1 and 16.5% of 11c,13t respectively.

* Contains 16.1 and 16.5% of 11c,13t respectively.

50 : 50 mixture of 9c,11t- and 10t,12c-18:2 isomers (Fig. 12.3). Later studies using single isomers enabled the determination of which isomer was the active one and which one(s) may have some adverse effects. A recent intervention study on humans published in 2005, for the first time compared a butter naturally low in CLA (0.4 g CLA/100 g butter) with a butter enriched in CLA (4.2 g CLA/100 g butter) (Desroches et al., 2005).

12.3.1 Animal studies

Many studies on different animal species such as mice, rats, and pigs (e.g. Ostrowska et al., 1999; Park et al., 1999b; Gavino et al., 2000; Bouthegourd et al., 2002; Evans et al., 2002; Wang and Jones, 2004), have shown that CLA may affect body composition, mainly by a reduction of body fat and sometimes by enhancement of fat-free mass (Fig. 12.4). It was also shown by feeding and withdrawing CLA in mice that the process is reversible, but the body fat accumulation in mice previously fed the CLA was smaller than that of the control and did not appear to return to control levels even after 8 weeks (Park et al., 1999a) when tissue CLA had returned to control levels. The effect of CLA on body composition was dependent on the species and mice seem to be the most reactive (Pariza et al., 2001). It was then demonstrated using fractions enriched with one or other isomer that body composition changes were associated with the 10t,12c-18:2 isomer (Park et al.,

9c,11t

9c,11t

Milk fatty acid methyl esters

trans, trans

Commercial CLA mixture

10t,12c

8/1Qf ^ 9c,11c 1Qc,12c trans, trans

Fig. 12.3 Gas liquid chromatographic analyses of CLA isomers in milk (top) and of a commercial CLA mixture (bottom) (P. Juaneda and J. L. Sebedio, unpublished data, 2002).

Fig. 12.4 Effect of feeding pure CLA and a CLA mixture on body composition of female mice; "significantly different from control and from 9c,11t (adapted from

Control 9c-11t- 10t-12c- CLA mix

Fig. 12.4 Effect of feeding pure CLA and a CLA mixture on body composition of female mice; "significantly different from control and from 9c,11t (adapted from

1999b). It was also found that CLA reduced fat deposition in male AKR/J mice fed either a low-fat diet or a high-fat diet (West et al., 1998). Studies carried out on animals, and also on cell cultures, have shown that the 10t,12c isomer may act at different levels (Pariza et al., 2001). CLA was reported to alter energy balance by increasing energy expenditure (West et al., 1998). In fully differentiated 3T3-L1 adipocytes, CLA supplementation was shown to reduce the lipoprotein lipase (LPL) activity, one of the key enzymes in lipid metabolism (Park et al., 1997). Treatment of 3T3-L1 adipocytes with the 10t,12c isomer also resulted in a dose-dependent decrease in the expression of the stearoyl coenzyme A (CoA) desaturase, an important enzyme in lipogenesis (Choi et al., 2000). The 10t,12c isomer also affects pre-adipocyte differentiation (Kang et al., 2003), inhibits proliferation, reduces triglyceride accumulation and induces apoptosis in 3T3-L1 pre-adipocytes (Evans et al., 2000).There are also in vivo data to support the suggestion that CLA supplementation reduces adipose tissues by apoptosis in mice (Tsuboyama-Kasaoka et al., 2000). Another study on rats also suggested that CLA reduced adipose tissue cell size rather than cell number (Azain et al., 2000).

12.3.2 Human studies

The data obtained from the human studies so far carried out do not give a clear picture compared with studies using the different animal models and it is therefore difficult to determine if any of the CLA isomers or a mixture of them have an effect on body composition in humans. As shown in Table 12.5, most of the studies differed in subject gender, initial body weight (obese and non-obese subjects), duration, the nature of the isomers, the length of the treatment, and also the methods utilised to evaluate the effect of the treatment. Most studies used isomers in gelatine capsules while one study (Malpuech-Brugere et al., 2004) used synthetic triacylglycerols in a functional food and another (Desroches et al., 2005) used a butter enriched in CLA in comparison with a butter low in CLA.

As an example, in obese men and women (Fig. 12.5) (Blankson et al., 2000), a decrease in fat mass was observed even at the lowest dosage (1.7 g/ day of mixed CLA), while an increase in lean body mass was only detected at the highest CLA dosage. However it is somewhat surprising that an intermediate amount (5.1 g/day) did not have any effect on body composition. Interestingly, in the study of Malpuech-Brugere et al. (2004) feeding the isolated isomers at 1.5 and 3.0 g/day for 18 weeks did not result in any changes in body composition in overweight men. In fact it is impossible to compare these two intervention studies considering the differences in the protocols. By looking at the results reported in Table 12.5, one may suggest that in non-obese subjects (body mass index, BMI <25), CLA has little or no effect on body composition, except in the study of Thom et al. (2001) where exercise was associated with the treatment. On the contrary, feeding

Table 12.5 Effect of feeding CLA on body composition in humans

Gender

BMI (kg/m2)

CLA (g/day)

Duration (weeks)

Effects

References

M/F

>30

2.8

24

Exercise effect

Atkinson, 1999

F

<25

3.9

9

No

Zambell et al., 2000

M/F

>25 and <35

1.7-6.8

12

■Fat mass

Blankson et al., 2000

M/F

30

3.4

12

No

Berven et al., 2000

M/F

<25

4.2

12

■13.8% fat mass

Smedman and Vessby,

M/F

<25

1.8

12

■4% fat mass

Thom et al., 2001

M/F

<30

0.7-1.4

4 + 4

■Fat mass

Mougios et al., 2001

M/F

>30

4.2

4

■Abdominal diameter

Riserus et al., 2001

25

6 + training

4

No

Kreider et al., 2002

F

<30

2.1

6

No

Petridou et al., 2003

M/F

28

Weight loss then

3

No effect of CLA on body

Kamphuis et al., 2003

1.8-3.6

13

weight regain

M

<30

1.5-3

18

No

Malpuech-Brugere et a

9c11t/10t,12c

M

>30

3

12

No

Riserus et al., 2004a

9c,11t

M

>30

0.6-2.4

13

No

Tricon et al., 2004

9c,11t/10t,12c

M/F

<30

3.6

52

■5 % fat mass

Gaullier et al., 2004

MF

30

3.4

(52) + 52

No effect after first 52

Gaullier et al., 2005

extension study

weeks on CLA

M

31

Butter enriched in

4 (cross-over)

No

Desroches et al., 2005

CLA vs butter low in CLA

CLA vs butter low in CLA

BMI, body mass index.

Fig. 12.5 Effect of feeding CLA on body composition of humans; *different from placebo (adapted from Blankson et al. (2000)).

Fig. 12.5 Effect of feeding CLA on body composition of humans; *different from placebo (adapted from Blankson et al. (2000)).

obese men with CLA most often resulted in a loss of fat mass but the effects were small if we consider the amount of isomers fed to the subjects (up to 6-7 g/day).

Only the studies of Gaullier et al. (2004, 2005) examined the long-term effects of feeding 3.4 g/day of a mixture of CLAs for two consecutive periods of 52 weeks. During the first period of 52 weeks CLA fed as free fatty acid or as triacylglycerol (CLA-TG) reduced the fat mass as well as body weight and BMI in both CLA groups, but only the CLA-TG group was different from the placebo for body weight and BMI. The same participants were included in an extension trial for another 52 weeks in order to evaluate the safety of using a CLA supplement for a long period. Feeding 3.4 g of CLA per day to volunteers who had already had the treatment for 52 weeks did not lead to further decrease in either fat mass or body weight. However, body weight and fat mass decreased in the subjects administered the placebo during the initial period.

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